Elevation of vascular endothelial growth factor-A serum levels following acute myocardial infarction. Evidence for its origin and functional significance

Following the onset of acute myocardial infarction (AMI), a number of serum parameters show well-defined changes reflecting myocardial injury. During the consecutive repair phase, compensatory processes are initiated includin g the formation of a collateral circulation on the basis of angiogenesis an d arteriogenesis. An important angiogenic factor is vascular endothelial gr owth factor-A (VEGF-A), shown to be upregulated in the ischemic myocardium, It is unclear, however, whether acute myocardial ischemia leads to a detec table elevation of VEGF-A serum concentrations. With the use of an immunoradiometric assay, we measured the levels of VEGF- A in the serum of patients after AMI at defined lime intervals, of patients with unstable angina pectoris (UAP) and of healthy individuals, In additio n, in a small group of patients with subacute myocardial infarction VEGF-A concentrations were measured in coronary sinus blood. The data are given as median followed by the 25th and 7th percentiles. In the group with AMI serum VEGF-A measured 105 [78: 176] pg/ml on day 1 an d 114 pg/ml [72; 163] pg/ ml on day 3 after onset of AMI. Serum levels of V EGF-A significantly increased on day 7 after AMI to 189 [119; 373] pg/ml (P = 0.0103) and on day 10 to 255 [162: 371] pg/ml (P = 0.0007). The VEGF-A s erum level in healthy controls and in patients with UAP measured 98 [75: 13 7] pg/ml and 116 [57; 140] pg/ml. respectively, Serum at day 10 after AMI c ontained VEGF-A at a biologically relevant concentration capable of stimula ting proliferation of endothelial cells. Surprisingly, VEGF-A serum levels were similar in samples taken from the coronary sinus with 61 [43; 83] pg/m l. Therefore the main source for VEGF-A in the blood stream is not the infa rcted myocardium. However, the number of platelets, a rich source of VEGF-A , is significantly increased after myocardial infarction, i.e. 284 [252: 36 3] x 10(9)/litre v 220 [177: 250] x 10(9)/litre. In conclusion, the time course of VEGF-A elevation following AMI strongly s uggests that VEGF-A plays a role as an endogenous activator of coronary col lateral formation in the human heart. The most likely source of the elevate d VEGF-A are platelets, rather than the infarcted myocardium. (C) 2000 Acad emic Press.